\ The targeting ability of pentapeptide (Thr-Lys-Pro-Pro-Arg) grafted nanostructured lipid carriers (Pen-NLCs) to macrophages was investigated in both in vitro and in vivo studies. The results showed the improvement of the anti-inflammatory effect by using this drug delivery system. Firstly, a pentapeptide-polyethylene glycol2000-stearate was synthesized and formulated into Pen-NLCs. Non-grafted nanostructured lipid carriers (Bare-NLCs) and Pen-NLCs were 190.0 + 1.0 and 203.0 + 8.5 nm in size, -8.1 +/- 2.1 and 2.3 +/- 1.2 mV in zeta potential respectively. Meanwhile, they had comparable entrapment efficiency and drug loading efficiency. In vitro and in vivo cellular uptake studies showed increased internalization of Pen-NLCs by macrophages when compared to pure drugs and Bare-NLCs. Animal studies in a carrageenan-treated air pouch model were used to further investigate the anti-inflammatory effects of Pen-NLCs. Through intravenous administration, a single dose of DXM loaded Pen-NLCs showed the strongest inhibition of inflammatory indexes of air pouch fluid weight, leukocyte infiltration, granulation tissue weight and nitric oxide concentration in comparison with free drugs and DXM loaded Bare-NLCs. In conclusion, this study demonstrated the potential of Pen-NLCs as promising drug carriers for anti-inflammatory treatments. (C) 2013 Elsevier B.V. All rights reserved.